Altitude sickness can occur in humans from a height of over 2500 m above sea level. At a height of over 2500 meters, the oxygen concentration and the air pressure decrease considerably. A differentiation is made between cerebral and pulmonary forms of acute altitude sickness. Acute altitude sickness therefore occurs in the brain and also in the lung. The first detailed clinical description of altitude sickness took place during a Mont Blanc expedition in 1891. At least four members of the expedition suffered from altitude sickness, with one member dying on 2 Sep. 1891 at a height of 4000 m. Since these cases, altitude sickness is deemed to be an individual life-threatening clinical condition.
If untreated, the pulmonary form of altitude sickness can lead to death in less than 24 hours, with death frequently occurring through a secondary pulmonary embolism.
The most effective treatment of all forms of acute altitude sickness is the supply of oxygen, for example by rapid descent of the sufferer to lower altitudes, or by means of bottled oxygen or by means of a portable hyperbaric chamber. However, in mountainous regions, a rapid descent is often not possible. Oxygen ventilation by e.g. bottled oxygen does indeed reduce the increased pulmonary arterial pressure, but does not normalize it. Also, in the case of a portable hyperbaric chamber, the positive effect is only temporary. The success of the therapy disappears in patients immediately after leaving the hyperbaric chamber, when they become physically active again.
A medicinal treatment for altitude sickness is currently only limited and controversial: Thus, dexamethasone is suggested in severe acute altitude sickness and also specifically in the cerebral form of altitude sickness. Furthermore, it has been discussed whether PDE-5 inhibitors, which are used for the treatment of primary pulmonary arterial hypertension (Dana Point Classification 1) are also indicated for secondary pulmonary hypertension through lack of oxygen at altitudes (Dana Point Classification 3).
Natural treatment possibilities for altitude sickness (also preventatively) were also proposed (tea from the leaves of the coca bush; yak butter tea; preparations which contain ginkgo as active ingredient).
However, it is to be noted that currently the possibility for medicinal treatment of the pulmonary form of altitude sickness is still very limited. Furthermore, it is known that organized rescue operations can only be counted upon in the European alpine region and partly also in the North American region. In remote high mountains of the world and in extreme altitudes, rescue operations and medical aid in emergencies (with the use of bottled oxygen or portable hyperbaric chamber) are scarcely possible. The provision of an efficient medicinal treatment of altitude sickness would therefore be urgently necessary, also as a component as emergency pack for mountaineers who may be at risk of developing altitude sickness.
In EP 2 009 023 A1 new peptides are proposed for the treatment of oedemas. These peptides are evaluated here by the “TEER” (“Transepithelial electrical resistance”) test using Calu-3 cells, which does not constitute an established test system for fluid clearance in pulmonary oedemas (pulmonary oedema fluid clearance). Calu-3 cells are in fact bronchial cells which only constitute approximately 1% of the surface of the lung serving for gas exchange. In contrast, alveolar cells constitute 99% of the surface of the lung serving for gas exchange (Hollenhorst et al., J. Biomed. Biotechnol. 2011 (2011), doi:10.1155/2011/174306). In contrast to the TEER test, the human alveolar epithelial cell line A549 is established as accepted experimental standard as a model for alveolar epithelial cells (Lazrak et al., Am. J. Physiol. Lung Cell. Mol. Physiol. 278 (2000), L848-57).
It is therefore an object of the present invention to distinctly improve the possibilities for the medicinal treatment of patients with the pulmonary form of altitude sickness and to make available a means by which this disease can be effectively treated, but also avoided.